This article analyzes the use of medicines and related perceptions among Guaraní Indians on the coast of Santa Catarina State, Brazil. The ethnographic research included participant observation, open and semi-structured interviews, and household surveys. Analyzing six months of prescriptions from 2008, 458 medicines were prescribed in 236 medical consultations, featuring cough and cold preparations, analgesics, and anti-helminthics, among drugs. In the three household surveys, analgesics and cough and cold preparations were the most frequently found in 2006 and 2007, while drugs for anemia were the most common in 2008. The Guaraní mainly used the primary healthcare services for colds, coughs, and diarrhea, and their practices also included turning to the shaman and self-care with medicines and herbal remedies, recognizing the efficacy of medicines and evaluating the treatment according to their experiences and their conceptions of the health-disease-care process. The study indicates the need for dialogue between professionals and users, linking the various forms of health knowledge.